Not applicable.
The invention is directed generally to improved apparatus for controlling and regulating the flow of fluids in microfluidic systems and particularly to devices that control and regulate fluid flow in microfluidic systems by means of a mobile, monolithic polymer element. The invention further includes methods for the manufacture of these monolithic polymer elements that provides for the polymer element to be cast-in-place in such a manner that the element will conform to the shape of the microchannel walls and not bond to the microchannel walls, thereby retaining mobility.
Recent advances in miniaturization have led to the development of microfluidic systems that are designed, in part, to perform a multitude of chemical and physical processes on a micro-scale. Typical applications include analytical and medical instrumentation, industrial process control equipment, and liquid and gas phase chromatography. In this context, there is a need for devices that have fast response times to provide very precise control over small flows as well as small volumes of fluid (liquid or gas) in microscale channels. In order to provide these advantages, it is necessary that the flow control devices be integrated into the microfluidic systems themselves. The term xe2x80x9cmicrofluidicxe2x80x9d refers to a system or device having channels or chambers that are generally fabricated on the micron or submicron scale, i.e., having at least one cross-sectional dimension in the range from about 0.1 xcexcm to about 500 xcexcm. Examples of methods of fabricating such microfluidic systems can be found in U.S. Pat. No. 5,194,133 to Clark et al., U.S. Pat. No. 5,132,012 to Miura et al., U.S. Pat. No. 4,908,112 to Pace, U.S. Pat. No. 5,571,410 to Swedberg et al., and U.S. Pat. No. 5,824,204 to Jerman.
Although there are numerous micro-fabricated valve designs that use a wide variety of actuation mechanisms (Shoji and Esashi, J. Micromech. Microeng., 4, 157-171, 1994), most dissipate relatively large amounts of power to the chip or substrate or require complex assembly which limits their use in practical systems. Most microvalves are manufactured from silicon and are therefore not easily integrated into non-silicon microchip platforms such as silica, glass, or synthetic materials such as organic polymers. A microvalve using an electromagnetic drive is described in U.S. Pat. No. 5,924,674 issued to Hahn et al. Jul. 20, 1999. Microvalves using thermopneumatic expansion as the actuation mechanism and a shape memory alloy diaphragm and bias spring are commercially available. However, these microvalves suffer from the fact that they consume relatively large amounts of power during operation, typically between 200 and 1500 mW depending upon the design. This high power consumption can be a significant disadvantage when heating of the fluid must be avoided, when batteries must supply power, or when the microvalve is placed on a microchip. Moreover, valves using the aforementioned actuation mechanisms can only generate modest actuation pressures. Perhaps most importantly, these valve designs can be difficult and costly to manufacture and assemble, frequently requiring assembly in a clean room environment.
Recognizing that the power requirements of conventional valves limited their use in practical systems, Beebe et al. (Nature, 404, 588-590, April 2000) describe a flow control system consisting of a hydrogel. The hydrogel valves provide local flow control by expanding or contracting when exposed to various pH levels. While eliminating the need for associated power supplies, these valves suffer from slow response times (≈8-10 sec) and are able to withstand only modest pressure differentials.
Unger et al. (Science, 288, 113-116, April 2000) describe an arrangement for controlling fluid flow in microchannels. Flow control is accomplished by the use of soft elastomer xe2x80x9ccontrol linesxe2x80x9d that intersect the microfluidic channels fabricated in an elastomeric substrate material. Applying pressure to the external surfaces of the control lines causes them to deform closing off that part of the channel they intersect. While eliminating the problem of power dissipation to the substrate, these valves require a microchannel having a specially shaped cross-section to seal properly. They also intrinsically require that pressure greater than in the channel be applied to the control line to keep the valve shut.
Ramsey in U.S. Pat. No. 5,858,195 provides for valveless microchip flow control by simultaneously applying a controlled electrical potential to an arrangement of intersecting reservoirs. The volume of material transported from one reservoir to another through an intersection is selectively controlled by the electric field in each intersecting channel. In addition to the need for elaborate switching and control of electrical potential, there are problems with leakage of fluid from one channel to another through the common intersection because there is no mechanical barrier to diffusion. Further, this flow control method has essentially no control over pressure-driven flow. For example, the flow control of a 10 mM aqueous buffer at pH 7, using a 1000V/cm electric field in round channels about 50 xcexcm in diameter, can be completely disrupted by a pressure gradient of only 0.1 psi/cm. Higher electric fields are generally prohibited because of rapid ohmic heating of the fluid. Furthermore, the presence of pH or conductivity gradients within the fluid can disrupt this valving scheme (Schultz-Lockyear et al., Electrophoresis, 20, 529-538, 1999).
Accordingly, the present invention is directed to a cast-in-place mobile monolithic polymer element or member and method of manufacture thereof, and devices for controlling and regulating fluid flow, including ionic current flow, that incorporate the novel mobile monolithic polymer element.
A microfluid control device, or microvalve can be made that comprises generally a cast-in-place, mobile monolithic polymer element, disposed within a microchannel, and driven by a displacing force that can be fluid (either liquid or gas) pressure or an electric field against a sealing surface, or retaining means that can be a constriction or a stop in the microchannel, to provide for control of fluid flow. As a means for controlling fluid flow, these devices possess the additional advantage that they can be used to effect pressure and electric field driven flows, eliminate or enhance diffusive or convective mixing, inject fixed quantities of fluid, and selectively divert flow from one channel to various other channels. They can also be used to isolate electric fields, and, as a consequence, locally isolate electroosmotic or electrophoretic flows.
The mobile monolith polymer element of the invention is not restricted to any particular shape or geometry except by the configuration of microchannel in which it functions and the requirement that it provide an effective seal against fluid flow for valving applications.
By providing a method for producing a monolithic polymer element that does not bond to surrounding structures, these polymer elements are free to move within the confines of a microchannel and can be translated within the microchannel by applying a displacing force, such as fluid pressure or an electric field to the polymer element. It is well known in the art, that if a mobile body within a microchannel has a surface charge density that is different from that of the walls of the microchannel, the body can be translated in the microchannel by the application of an electric field. Hence, translation of the polymer element can be achieved by application of electric fields.
By means of the invention, it is now possible to manufacture a family of fluid flow control, regulation, and distribution devices such as, but not limited to, microvalves, nano- and pico-liter pipettes and syringes needle valves, diverter valves, and water wheel flowmeters.
In contrast to the prior art, the microfluid control devices, or microvalves, disclosed herein can seal against pressures greater than 5000 psi, dissipate no heat to a substrate, and have a response time on the order of milliseconds. Calculations show that a monolithic polymer element 50 xcexcm in diameter and 200 xcexcm long, with a 0.1 xcexcm gap between the element and the wall has an actuation time (for a pressure differential across the element of about 1 psi) of about 1.1 msec.
The polymer element of the microfluid control devices can be made by a one-step lithography process employing a polymer material that is polymerized by radiation, such as by thermal, visible, or UV radiation. Electrostatic attraction between microchannel walls and the polymer element that could influence the mobility of the polymer element is of particular concern. However, by providing for the polymer and microchannel surfaces to have the same, or no, electric charge it has been found that the monolithic polymer element will not bond with or be attracted to the microchannel wall. Thus, the element can be moved back and forth freely within the microchannel by application of pressure to either end of the element, i.e., by developing a pressure differential across the polymer element. The profile of the polymer element can be further configured by the directed application of radiation, preferably from a laser, to selected regions of the actuator causing the polymer in the irradiated regions to depolymerize. This can include, by way of example, making the middle part of the actuator narrower than the ends or vice versa. Because the monolithic polymer element can be manufactured in-place within minutes the microfluid control devices that employ them do not require expensive and complicated manufacturing and/or assembly processes.